ObjectiveThe unprecedented coronavirus disease 2019 (COVID-19) outbreak has resulted in a global crisis that negatively impacted physical well-being and mental health. Our goal was to investigate the impact of the COVID-19 pandemic on health-related quality of life (HRQoL) and depressive symptoms in patients with chronic diseases and the general population in Korea.MethodsData from 8341 patients with chronic diseases and 12,395 general population aged ≥20 years who participated in the Korea National Health and Nutrition Examination Survey (2017–2020) were analyzed. Patients with hypertension, dyslipidemia, diabetes, cerebrovascular disease (stroke), heart disease (myocardial infarction or angina pectoris), or cancer were classified as patients with chronic diseases. The general population was defined as those not suffering from corresponding chronic diseases. A modified EuroQol-5 Dimensions (EQ-5D), with three levels (0: extreme problems; 0.5: some problems; 1: no problems) for each dimension in EQ-5D, was used to assess HRQoL. To analyze depressive symptoms among patients with chronic diseases and the general population, we used the Patient Health Questionnaire-9 (PHQ-9) and defined a PHQ-9 score ≥ 10 as having a depressive symptom. Multivariate linear and logistic regression analyses were used to analyze HRQoL and depressive symptoms before and during the COVID-19 pandemic.ResultsThe HRQoL level was significantly lower in patients with chronic diseases compared to the general population on all dimensions both before and during the COVID-19 pandemic (all value of p < 0.05). Patients with chronic diseases had significantly lower HRQoL levels associated with the anxiety/depression dimension during the COVID-19 pandemic than in the pre-pandemic period (0.940 ± 0.002 vs. 0.929 ± 0.004, value of p = 0.041). In addition, patients with chronic diseases were more likely to report depressive symptoms during the COVID-19 pandemic than in the pre-pandemic period (Odds ratio (OR): 1.755, 95% confidence interval (CI): 1.209–2.546, value of p = 0.003). However, this association was not observed in the general population (OR: 1.275, 95% CI: 0.933–1.742, value of p = 0.13).ConclusionThe COVID-19 pandemic affected the HRQoL and psychological health in patients with chronic diseases with higher anxiety/depression during the pandemic than in the pre-pandemic period. These results suggest that it is urgent to establish continuous management guidelines, including psychosocial management for high-risk groups, and to improve the existing healthcare system.